Perspectives on the assessment of human sperm chromatin integrity

Palermo, Gianpiero D.; Neri, Q.V.; Cozzubbo, T.; Rosenwaks, Zev

doi:10.1016/j.fertnstert.2014.10.008

Cited by 80 publications

(68 citation statements)

References 94 publications

(138 reference statements)

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“…Their results provided clear support for this hypothesis and showed that the epithelial cells were actively able to discriminate between spermatozoa carrying normal or unstable chromatin. These results are in accordance with an earlier study of human spermatozoa [40] showing that cervical mucus could act as a barrier against the progress of DNA-damaged cells, possibly because the DNA-damaged cells are less motile [41]. The importance of sperm-oviduct epithelial cell binding in controlling sperm quality has been reported in other in vitro studies [42][43][44][45][46][47] and has been proposed as a method for predicting fertility in cows [48] and pigs [49].…”

Section: Sperm Dna and Oviductal Interactionssupporting

confidence: 91%

Sperm selection in the female mammalian reproductive tract. Focus on the oviduct: Hypotheses, mechanisms, and new opportunities

Holt¹,

Fazeli²

2016

Theriogenology

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Section: Sperm Dna and Oviductal Interactionssupporting

confidence: 91%

Sperm selection in the female mammalian reproductive tract. Focus on the oviduct: Hypotheses, mechanisms, and new opportunities

Holt¹,

Fazeli²

2016

Theriogenology

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“…The SCSA bases its results on (1) the DNA fragmentation index (DFI), which is the percentage in the sample that have measurable increased red fluorescence due to acridine orange attaching to a single strand portion of DNA at sites of DNA strand breaks and then collapsing into a crystal that produces a metachromatic shift to red fluorescence under exposure to blue light and (2) the percentage of high DNA stainability (HDS), which is due to excess histones and proteins other than protamines that prevent full condensation of the sperm chromatin [30–32]. …”

Section: Introductionmentioning

confidence: 99%

Measuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis

et al. 2016

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Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to test sperm DNA fragmentation such as the sperm chromatin structure assay (SCSA), the sperm chromatin dispersion (SCD) test, the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay and the single cell gel electrophoresis (Comet) assay. We performed a systematic review and meta-analysis to assess the value of measuring sperm DNA fragmentation in predicting chance of ongoing pregnancy with IVF or ICSI. Out of 658 unique studies, 30 had extractable data and were thus included in the meta-analysis. Overall, the sperm DNA fragmentation tests had a reasonable to good sensitivity. A wide variety of other factors may also affect the IVF/ICSI outcome, reflected by limited to very low specificity. The constructed hierarchical summary receiver operating characteristic (HSROC) curve indicated a fair discriminatory capacity of the TUNEL assay (area under the curve (AUC) of 0.71; 95% CI 0.66 to 0.74) and Comet assay (AUC of 0.73; 95% CI 0.19 to 0.97). The SCSA and the SCD test had poor predictive capacity. Importantly, for the TUNEL assay, SCD test and Comet assay, meta-regression showed no differences in predictive value between IVF and ICSI. For the SCSA meta-regression indicated the predictive values for IVF and ICSI were different. The present review suggests that current sperm DNA fragmentation tests have limited capacity to predict the chance of pregnancy in the context of MAR. Furthermore, sperm DNA fragmentation tests have little or no difference in predictive value between IVF and ICSI. At this moment, there is insufficient evidence to recommend the routine use of sperm DNA fragmentation tests in couples undergoing MAR both for the prediction of pregnancy and for the choice of treatment. Given the significant limitations of the evidence and the methodological weakness and design of the included studies, we do urge for further research on the predictive value of sperm DNA fragmentation for the chance of pregnancy after MAR, also in comparison with other predictors of pregnancy after MAR.

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“…Several different assays are in use including indirect methods such as sperm chromatin structure assay (SCSA) (Evenson et al, 1980) and sperm chromatin dispersion assay (Fernandez et al, 2003), and direct methods such as Comet (Hughes et al, 1996) and TUNEL assays (Gorczyca et al, 1993). The most frequently used method is SCSA, which assesses the susceptibility of spermatozoa to induced DNA damage as indicated by incorporation of acridine orange and measured by flow cytometry (Evenson, 2013;Palermo et al, 2014). Results are reported as DNA fragmentation index (DFI), the percentage of spermatozoa with a red (denatured single-stranded DNA) to green (native doublestranded DNA) fluorescence ratio above a threshold that is indicative of DNA damage, with the cutoff for subfertility typically set around DFI 25-30% (Evenson et al, 1999;Evenson, 2013).…”

Section: Introductionmentioning

confidence: 99%

Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis

Bradley¹,

McArthur²,

Gee³

et al. 2016

Andrology

105

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SUMMARYSperm DNA fragmentation (SDF) is used in assisted reproductive technology (ART) programs as an indicator for sperm quality, although there is still a lack of consensus as to its clinical utility. In this retrospective study, we examined intracytoplasmic sperm injection (ICSI) outcomes of 1924 infertile patients who underwent SDF analysis using the sperm chromatin integrity test. ART patients were classified as having low [DNA fragmentation index (DFI) <29%] or high SDF (DFI ≥29%) and by whether or not an intervention [physiological intracytoplasmic sperm injection (PICSI), intracytoplasmic morphologically selected sperm injection (IMSI), testicular sperm extraction (TESE)/testicular sperm aspiration (TESA), frequent ejaculation] was performed. High SDF patients who did not have an intervention had a lower fertilization rate and poorer clinical outcomes from blastocyst transfers as compared with low SDF patients; the fertilization rate was 66.0% vs. 70.2% (p = 0.042), single embryo transfer (SET) fetal heart pregnancy rate was 28.5% vs. 45.2% (p = 0.042), and SET live birth rate was 24.9% vs. 40.6% (p = 0.060), respectively. Furthermore, high SDF patients who had an intervention had significantly improved blastocyst transfer outcomes, similar to those of low SDF patients; the SET live birth rate for high SDF intervention patients was 43.8% as compared with 24.9% for high SDF no intervention patients (p = 0.037) and 40.6% for low SDF patients (p = 0.446). Analysis of the three main intervention subgroups for high SDF patients revealed that TESE/TESA patients had the highest SET live birth rate; in comparison with 24.2% for high SDF patients who did not have an intervention, PICSI patients had 38.3% (p = 0.151), IMSI patients had 28.7% (p = 0.680), and TESE/TESA patients had 49.8% (p = 0.020). Our data suggest that SDF results indicate ICSI outcomes and that patients who have high SDF benefit from an intervention.

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Perspectives on the assessment of human sperm chromatin integrity

Cited by 80 publications

References 94 publications

Sperm selection in the female mammalian reproductive tract. Focus on the oviduct: Hypotheses, mechanisms, and new opportunities

Sperm selection in the female mammalian reproductive tract. Focus on the oviduct: Hypotheses, mechanisms, and new opportunities

Measuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis

Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis

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